The objective of this proposal is to study the effect of growth factors, such as nerve growth factor, on neural regeneration in the damaged mammalian cochlea. This information has important clinical implications for individuals with profound bilateral sensorineural hearing loss who are candidates for cochlear implantation. One limitation in the successful use of implants is the extent of preexisting damage in the implanted cochlea. If the sensory and/or neural elements could be stimulated to regenerate, performance may be improved. Bohne and Harding (1992) recently described regenerated nerve fibers in the noise-damaged chinchilla cochlea. Ongoing studies in Bohne's laboratory are looking at the origin, bilateral symmetry, and long-term survivability of regenerated nerve fibers. Recent data indicate that most of these regenerated nerve fibers are afferent (Strominger et al., 1993). Activation of the electrodes in cochlear implants is thought to stimulate spiral ganglion cell bodies and/or their peripheral processes (e.g., Clopton et al., 1980; Fayad et al., 1991; Hinojosa and Lindsay, 1980). If the condition of the surviving spiral ganglion cells in profoundly deaf individuals could be enhanced by treatment with exogenous growth factors, perhaps auditory performance with an implant could be improved. Basic fibroblast growth factor, transforming growth factor and nerve growth factor have been shown to stimulate survival and sprouting of spiral ganglion cells in dissociated culture of adult rat cochlea (Lefebvre et al., 1991). It is the effect of these growth factors on the regenerated nerve fibers that we propose to study. Animals will be exposed binaurally for 12 hours to an octave band of noise with a center frequency of 0.5 kHz and a sound pressure level of 120 dB. An implantable osmotic pump will be used to deliver growth factor to one cochlea during the period of neural regeneration and recovery. The other ear will used as a control. Using a combined organ of Corti/modiolus dissection technique the organ of Corti and spiral ganglion from both cochleas will be histologically examined and the number of regenerated nerve fibers quantified.